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UC: Efficacy and Safety Study of Apremilast to Treat Active Ulcerative Colitis

Sponsor
Amgen (Industry)
Overall Status
Completed
CT.gov ID
NCT02289417
Collaborator
(none)
170
Enrollment
99
Locations
3
Arms
52.8
Actual Duration (Months)
1.7
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the clinical efficacy, safety and tolerability of apremilast (30 mg twice daily [BID] and 40 mg BID), compared with placebo, in participants with active Ulcerative Colitis (UC).

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Approximately 165 participants (55 subjects per arm) will be randomized in a 1:1:1 ratio to receive oral apremilast (30 mg BID or 40 mg BID), or identically appearing placebo BID for up to 12 weeks, followed by 40 weeks of blinded treatment with apremilast (30 mg BID or 40 mg BID).

At the end of the Blinded Active-treatment Phase (Week 52), participants who have a Mayo endoscopy score ≤ 1 will have the opportunity to participate in the Extension Phase. Participants enrolled in the Extension Phase will receive apremilast for an additional 52 weeks (Weeks 52 to 104). With the implementation of Amendment 4, participants entering the Extension Phase will receive apremilast 30 mg BID. Subjects currently in the Extension Phase who are receiving apremilast 40 mg BID will be switched to 30 mg BID at the next scheduled visit.

Study Design

Study Type:
Interventional
Actual Enrollment :
170 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Randomized, Placebo-controlled, Multicenter Study to Investigate the Efficacy and Safety of Apremilast (CC-10004) for Treatment of Subjects With Active Ulcerative Colitis
Actual Study Start Date :
Jan 8, 2015
Actual Primary Completion Date :
Sep 25, 2017
Actual Study Completion Date :
Jun 3, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Apremilast 30 mg PO BID

Apremilast 30 mg by mouth (PO) twice a day (BID) for 12 weeks After 12 weeks: Participants who achieve at least a 20% decrease from baseline in the total Mayo score (TMS) will continue to receive apremilast 30 mg BID for an additional 40 weeks. (Wk 52) Participants who do not achieve at least a 20% decrease from baseline in the TMS will receive apremilast 40 mg BID for an additional 40 weeks (Wk 52) After 52 weeks, participants who are eligible for the Extension Phase will continue to receive the same dose of apremilast assigned at Wk 12 (30 mg BID or 40 mg BID) for an additional 52 weeks (Wk 104)

Drug: Apremilast
Other Names:
  • CC-10004; Otezla

    		•
    Experimental: Apremilast 40 mg PO BID

    Apremilast 40 mg by mouth (PO) twice a day (BID) for 12 weeks After 12 weeks, participants assigned to the 40 mg BID dose of apremilast at baseline will continue to receive apremilast 40 mg BID for an additional 40 weeks (Wk 52) After 52 weeks, participants who are eligible for the extension Phase will continue to receive apremilast 40 mg BID for an additional 52 weeks (Wk 104)

    Drug: Apremilast
    Other Names:
  • CC-10004; Otezla

    		•
    Placebo Comparator: Placebo BID

    Identically matching placebo by mouth (PO) twice a day (BID) for 12 weeks. After 12 weeks all participants randomized to placebo at baseline will be re-randomized to receive apremilast 30 mg or 40 mg BID for an additional 40 weeks (Wk 52) After Wk 52, participants who are eligible for the extension phase will continue to receive the same dose of apremilast assigned at Wk 12 (30 mg BID or 40 mg BID) for an additional 52 weeks (Wk 104)

    Drug: Apremilast
    Other Names:
  • CC-10004; Otezla

    • Drug: Placebo

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Who Achieved a Clinical Remission by Total Mayo Score (TMS) at Week 12 [Week 12]

      Clinical remission was defined as a total Mayo score ≤ 2 points, with no individual subscore exceeding 1 point. The TMS is an instrument designed to measure disease activity of UC. The Mayo score ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease. Stool Frequency Subscore (SFS) Rectal Bleeding Subscore (RBS) Endoscopy Subscore Physician's Global Assessment (PGA). Two-sided 95% confidence intervals (CI) for the within-group percentages are based on the Wilson score method.

    Secondary Outcome Measures

    1. Percentage of Participants Who Achieved a Clinical Response by Total Mayo Score and the Reduction in the Rectal Bleeding Subscore at Week 12 [Week 12]

      Clinical response was defined as a decrease from baseline in the TMS of at least 3 points and at least 30%, along with a reduction in the rectal bleeding subscore (RBS) of at least 1 point or an absolute RBS of ≤ 1. The TMS is an instrument designed to measure disease activity of UC. The Mayo score ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease. Stool Frequency Subscore (SFS) Rectal Bleeding Subscore Endoscopy Subscore Physician's Global Assessment (PGA) Rectal bleeding (subscore 0-3) was defined as: 0 = No blood seen = Streaks of blood with stool less than half the time = Obvious blood with stool = Blood alone passes Two-sided 95% CI for the within-group percentages are based on the Wilson score method.

    2. Percentage of Participants Who Achieved an Endoscopic Remission at Week 12 [Week 12]

      An endoscopic remission was defined as a Mayo endoscopic subscore (MES) of 0 at Week 12. The MES subscore findings were defined as: 0 = Normal or inactive disease = Mild Disease (erythema, decreased vascular pattern, mild friability) = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions) = Severe Disease (spontaneous bleeding, ulceration) The endoscopy subscores consisted of findings that were centrally read through proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method.

    3. Percentage of Participants Who Achieved an Endoscopic Response at Week 12 [Week 12]

      An endoscopic response is defined as a decrease from baseline of at least 1 point in the MES at Week 12. The Mayo endoscopy subscore findings were defined as: 0 = Normal or inactive disease = Mild Disease (erythema, decreased vascular pattern, mild friability) = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions) 3 = Severe Disease (spontaneous bleeding, ulceration). The endoscopy subscores consisted of findings that were centrally read through proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method.

    4. Percentage of Participants Who Achieved a Rectal Bleeding Subscore (RBS) of ≤ 1 at Week 12 [Week 12]

      The RBS was measured as: 0 = No blood seen = Streaks of blood with stool less than half the time = Obvious blood with stool most of the time = Blood alone passes The daily bleeding score represents the most severe bleeding of the day. Two-sided 95% CI for the within-group proportions are based on the Wilson score method.

    5. Percentage of Participants Who Achieved Clinical Remission in the Modified Mayo Subscore (MMS) at Week 12 [Week 12]

      Clinical remission was defined as a modified Mayo score of ≤ 2, with no individual subscore > 1, at Week 12. The MMS was based on a modification of the total Mayo score (TMS) which included the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the Physician's Global Assessment (PGA) subscore, since this was a global measure that is subjective in nature. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity. The endoscopy subscores was centrally reviewed. Two-sided confidence intervals for the within-group percentage were based on the Wilson score method.

    6. Percentage of Participants Who Achieved Clinical Response in the Modified Mayo Subscore (MMS) at Week 12 [Week 12]

      Clinical response in the MMS was defined as a decrease from baseline in the MMS of at least 2 points and at least 25%, along with a reduction in the RBS of at least 1 point or an absolute RBS ≤ 1. The MMS was based on the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the PGA subscore. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity. The RBS was measured as: 0 = No blood seen = Streaks of blood with stool less than half the time = Obvious blood with stool most of the time = Blood alone passes The daily bleeding score represents the most severe bleeding of the day. The endoscopy subscores was centrally reviewed. Two-sided confidence intervals for the within-group percentage were based on the Wilson score method.

    7. Percentage of Participants Who Achieved Clinical Remission in the Partial Mayo Subscore (PMS) With no Individual Subscore >1 at Week 8 [Week 8]

      Clinical remission in the partial Mayo subscore was defined as a PMS of 2 points or lower, with no individual subscore >1. The PMS is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease). Two-sided 95% CI for the within-group proportions are based on the Wilson score method.

    8. Percentage of Participants Who Achieved Clinical Response in the Partial Mayo Subscore at Week 8 [Week 8]

      Clinical response in the PMS was defined as a decrease from baseline in PMS of at least 2 points and at least 25%, with an accompanying decrease in the RBS of at least 1 point or an absolute RBS of 0 or 1. The PMS score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease). Two-sided 95% CI for the within-group proportions are based on the Wilson score method.

    9. The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase [From the first dose of investigational product (IP) and no later than 28 days after the last dose of IP for those who had completed the study or discontinued (D/C) early; maximum duration of exposure to treatment was 12.00 weeks]

      A TEAE was defined as any adverse event (AE) occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain

    10. The Number of Participants Who Discontinued Apremilast Due to Treatment Emergent Adverse Events During the Placebo-Controlled Period [From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early; median duration of exposure to treatment was 12.00 weeks]

      A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain.

    11. The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 [From first dose of IP and no later than 28 days after last dose of IP for those who completed the active treatment phase or D/C early; median duration of exposure = 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms]

      A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain

    12. The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) [From the first dose of IP at Week 52 and no later than 28 days after the last dose of IP for those who completed the study or had discontinued early; median exposure of apremilast for the total apremilast group was 52 weeks.]

      A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    Subjects must satisfy the following criteria to be enrolled in the study:

    • Male or female aged 18 and over at the time of signing the informed consent.

    • Must understand and voluntarily sign an informed consent form prior to any study related assessments/procedures being conducted.

    • Diagnosis of ulcerative colitis (UC) with a duration of at least 3 months prior to the Screening Visit..

    • Total Mayo Score (TMS) ≥ 6 to ≤ 11 (range: 0-12) at baseline, prior to randomization in the study.

    • Endoscopic subscore ≥ 2 (range: 0-3) on the Mayo score prior to randomization in the study.

    • Subjects must have had a therapeutic failure, been intolerant to, or have a contraindication to, at least one of the following: oral aminosalicylates (ie, 5-aminosalicylic acid [5-ASA] compounds or sulfasalazine [SSZ]), budesonide, systemic corticosteroids, or immunosuppressants (eg, 6-mercaptopurine [6-MP], azathioprine [AZA], or methotrexate [MTX]).

    Exclusion Criteria:
    The presence of any of the following will exclude a subject from enrollment:

    • Diagnosis of Crohn's disease, indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis or diverticular disease-associated colitis.

    • Ulcerative colitis restricted to the distal 15 cm or less (eg, ulcerative proctitis).

    • Subjects who have had surgery as a treatment for UC or who, in the opinion of the Investigator, are likely to require surgery for UC during the study.

    • Clinical signs suggestive of fulminant colitis or toxic megacolon.

    • Prior use of any tumor necrosing factor (TNF) inhibitor (or any biologic agent).

    • Prior use of mycophenolic acid, tacrolimus, sirolimus, cyclosporine or thalidomide.

    • Use of intravenous (IV) corticosteroids within 2 weeks of the Screening Visit.

    • Use of immunosuppressants (AZA, 6-MP or MTX) within 8 weeks of the Screening Visit.

    • Use of topical treatment with 5-ASA or corticosteroid enemas or suppositories within 2 weeks of the Screening Visit.

    • History of any clinically significant neurological, renal, hepatic, gastrointestinal, pulmonary, metabolic, cardiovascular, psychiatric, endocrine, hematological disorder or disease, or any other medical condition that, in the investigator's opinion, would preclude participation in the study.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Digestive Health Specialists of The Southeast Dothan Alabama United States 36305
    2 Southern California Research Institute Medical Group, Inc. Los Angeles California United States 90045
    3 Connecticut Clinical Research Foundation Bristol Connecticut United States 06010
    4 Consultants for Clinical Research of South Florida Boynton Beach Florida United States 33426
    5 Avail Clinical Research, LLC DeLand Florida United States 32720
    6 Precision Clinical Research, LLC Lauderdale Lakes Florida United States 33319
    7 Pharmax Research Clinic, Inc. Miami Florida United States 33126
    8 Gastroenterology Group of Naples Naples Florida United States 34102
    9 Advanced Medical Research Center Port Orange Florida United States 32127
    10 University of Chicago Medical Center Chicago Illinois United States 60637
    11 University of Iowa Hospitals and Clinics Iowa City Iowa United States 52242
    12 University of Louisville Louisville Kentucky United States 40202
    13 UMass Medical Center Worcester Massachusetts United States 01655
    14 Clinical Research Institute of Michigan, LLC Chesterfield Michigan United States 48047
    15 Center for Digestive Health Research Troy Michigan United States 48098
    16 Gastrointestinal Associates PA Flowood Mississippi United States 39232
    17 NYU Langone Long Island Clinical Research Associates Great Neck New York United States 11021
    18 Consultants for Clinical Research Cincinnati Ohio United States 45219
    19 Quality Medical Research Nashville Tennessee United States 37211
    20 Digestive Research Center/ Gastroenterology Consultants of San Antonio Live Oak Texas United States 78233
    21 Digestive Health Specialist of Tyler Pasadena Texas United States 77505
    22 San Antonio Gastroenterology San Antonio Texas United States 78229
    23 University of Utah Salt Lake City Utah United States 84132
    24 Harborview Medical Center Seattle Washington United States 98104
    25 University of Washington Medical Center Seattle Washington United States 98195
    26 Concord Repatriation General Hospital Concord New South Wales Australia 2139
    27 Liverpool Hospital Liverpool New South Wales Australia 2170
    28 Mater Adult Hospital South Brisbane Queensland Australia 4101
    29 Footscray Hospital Footscray Victoria Australia 3011
    30 Royal Melbourne Hospital Parkville Victoria Australia 3050
    31 Multiprofile Hospital for Active Treatment Kaspela Plovdiv Bulgaria 4002
    32 Medical Center Asklepion - Humane Medicine Research EOOD Sofia Bulgaria 1303
    33 University Multiprofile Hospital for Active Treatment ACIBADEM City Clinic Sofia Sofia Bulgaria 1407
    34 University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD Sofia Bulgaria 1431
    35 University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna ISUL EAD Sofia Bulgaria 1527
    36 Clinic of Gastroenterology Sofia Bulgaria 1784
    37 Multiprofile Hospital for Active Treatment Sveta Marina EAD Varna Bulgaria 9010
    38 Winnipeg Regional Health Authority - Health Sciences Centre Winnipeg Manitoba Canada R3A 1R9
    39 Hamilton Health Sciences Corporation, McMaster University Medical Centre Hamilton Ontario Canada L8N 3Z5
    40 Fakultni nemocnice u sv Anny v Brne Brno Czechia 656 91
    41 Fakultni nemocnice Hradec Kralove Hradec Kralove Czechia 500 05
    42 Hepato-Gastroenterologie HK, s. r. o. Hradec Králové Czechia 500 12
    43 Nemocnice Slany Slany Czechia 274 01
    44 Amiens University Hospital Amiens France 80054
    45 Hopital Beaujon Clichy France 92110
    46 CHRU Nantes Nantes France 602 00
    47 CHU de Nice Archet I Nice France 06202
    48 Centre Hospitalier Lyon Sud Pierre Bénite France 69495
    49 Centre Hospitalier Universitaire de Saint Etienne Saint Priest en Jarez France 42055
    50 CHRU Nancy Vandoeuvre les Nancy France 54511
    51 DRK Kliniken Berlin Westend Berlin Germany 14050
    52 Crohn-Colitis-Centre Rhein-Main Frankfurt Germany 60594
    53 Universitatsklinikum Schleswig-Holstein Keil Germany 24105
    54 Gastroenterologische Praxis Minden Minden Germany 32423
    55 Pannónia Magánorvosi Centrum Kft. Budapest Hungary 1136
    56 ENDOMEDIX Kft. Budapest Hungary 1139
    57 Vasútegészségügyi Nonprofit Kiemelten Közhasznú Kft. Debreceni Egészségügyi Központja Debrecen Hungary 4025
    58 Karolina Korhaz Rendelointezet Mosonmagyaróvár Hungary 9200
    59 Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont Szeged Hungary 6720
    60 Tolna Megyei Balassa Janos Korhaz Szekszárd Hungary 7100
    61 Javorszky Odon Korhaz Vác Hungary 2600
    62 Azienda Ospedaliero Universitaria Di Bologna Policlinico Sorsola Malpighi Bologna Italy 40138
    63 IRCCS - Istituo Clinico Humanitas - Humanitas Cancer Center Milan Italy 20089
    64 Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello Palermo Italy 90146
    65 Fondazione PTV Policlinico Tor Vergata Roma Italy 00133
    66 Complesso Integrato Columbus Roma Italy 00168
    67 Universitair Medisch Centrum Groningen Groningen Netherlands 9713 GZ
    68 Ikazia Ziekenhuis Rotterdam Netherlands 3083 AN
    69 Auckland City Hospital Auckland New Zealand 1023
    70 Christchurch Hospital Christchurch New Zealand 8011
    71 Dunedin Hospital Dunedin New Zealand 9016
    72 Waikato hospital Hamilton New Zealand 3204
    73 Uniwersytecki Szpital Kliniczny w Bialymstoku Bialystok Poland 15-276
    74 Osrodek Badan Klinicznych CLINSANTE S.C. Bydgoszcz Poland 85-794
    75 Centrum Medyczne sw. Lukasza Czestochowa Poland 42 202
    76 Economicus - NZOZ ALL-MEDICUS Katowice Poland 40 659
    77 Endoskopia Sp. z o.o. Sopot Poland 81-756
    78 Sonomed Sp. z o.o. Szczecin Poland 71-685
    79 Gastromed Kopon Zmudzinski i Wspolnicy Sp. j. Specjalistyczne Centrum Gastrologii i Endoskopii Spec. Gabinety Lekarskie Torun Poland 40 659
    80 Centrum Zdrowia Matki, Dziecka i Mlodziezy Warsaw Poland 00-632
    81 Niepubliczny Zaklad Opieki Zdrowotnej VIVAMED Warszawa Poland 03-563
    82 Lexmedica Drubajlo Hanna Wroclaw Poland 03-580
    83 Ars Medica Wroclaw Poland 53-333
    84 Republican Clinical Hospital Kazan Russian Federation 420064
    85 Stolitsa-Medikl, LLC Moscow Russian Federation 115088
    86 SEIHPE Rostov State Medical University of MoH of RF Rostov on Don Russian Federation 344022
    87 Regional Clinical Hospital Saratov Russian Federation 410053
    88 Russian Medical Military Academy na SMKirov St Petersburg Russian Federation 129329
    89 Regional Clinical Hospital, Gastroenterology department, State Higher Education Institute Ivano-Frankivsk National Medical University Ivano-Frankivsk Ukraine 58001
    90 Ivano-Frankivsk Regional Clinical Hospital Ivano-Frankivsk Ukraine 76008
    91 Ivano-Frankivsk Central City Clinical Hospital Ivano-Frankivsk Ukraine 76018
    92 Kharkiv City Clinical Hospital 2 Kharkiv Ukraine 61037
    93 Private Enterprise Private Manufacture Company Acinus Kirovograd Ukraine 25006
    94 Kremenchuk City Hospital # 1 n.a O.T.Bohaievskyi Kremenchuk Ukraine 39617
    95 Lviv Emergency Clinical Hospital, Therapeutics Department No. 1 Lviv Ukraine 79059
    96 Municipal Institution Odesa Regional Clinical Hospital Odesa Ukraine 65025
    97 Central City Clinical Hospital Uzhgorod Ukraine 88000
    98 Vinnytsia Regional Clinical Hospital n a M I Pyrohov Vinnytsia Ukraine 21018
    99 Municipal Institution Zaporizhzhia Zaporizhzhia Ukraine 69600

    Sponsors and Collaborators

    • Amgen

    Investigators

    • Study Director: MD, Amgen

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Amgen
    ClinicalTrials.gov Identifier:
    NCT02289417
    Other Study ID Numbers:
    • CC-10004-UC-001
    • 2014-002981-64
    First Posted:
    Nov 13, 2014
    Last Update Posted:
    May 7, 2020
    Last Verified:
    Apr 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by Amgen
    Ulcerative Colitis
    Inflammatory Bowel Disease
    Additional relevant MeSH terms:
    Colitis
    Colitis, Ulcerative
    Ulcer
    Apremilast

    Study Results

    Participant Flow

    Recruitment Details The study was conducted at 61 sites in Australia (3 sites) and New Zealand (1 site); Bulgaria (6 sites), Czech Republic (2 sites), Hungary (3 sites), Poland (9 sites), Russia (1 site), and Ukraine (10 sites); Canada (2 sites) and United States (13 sites); and France (4 sites), Germany (1 site), Italy (4 sites), and the Netherlands (2 sites).
    Pre-assignment Detail A total of 170 participants were randomized in a 1:1:1 ratio and received apremilast (30 mg BID or 40 mg BID), or identically appearing placebo and stratified based on concomitant use of oral corticosteroids and previous exposure to immunosuppressants.
    Arm/Group Title Placebo Apremilast 30 mg Apremilast 40 mg Placebo/Apremilast 30 mg Placebo/Apremilast 40 mg Apremilast 30 mg/Apremilast 40 mg Apremilast 40 mg/ Apremilast 40 mg Extension Phase: Apremilast 30 mg Extension Phase Apremilast 40 mg
    Arm/Group Description Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. At week 12, participants who achieved at least a 20% decrease from baseline in the total Mayo score (TMS) continued to receive 30 mg apremilast capsules BID for an additional 40 weeks during the active treatment phase. Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. At week 12, participants who achieved at least a 20% decrease from baseline in the TMS continued to receive 40 mg apremilast capsules BID for an additional 40 weeks during the active treatment phase. Participants initially randomized to placebo capsules in the placebo-controlled period were re-randomized at week 12 to receive 30 mg apremilast capsules BID for 40 weeks during the active treatment phase. Participants initially randomized to placebo in the placebo-controlled period were re-randomized at week 12 to receive 40 mg apremilast capsules BID for 40 weeks during the active treatment phase. Participants initially randomized to 30 mg apremilast capsules BID in the placebo-controlled phase who did not achieve at least a 20% decrease from baseline in the TMS were re-assigned to 40 mg apremilast capsules BID for 40 weeks during the active treatment phase. Participants initially randomized to 40 mg apremilast capsules BID in the placebo-controlled phase who did not achieve at least a 20% decrease from baseline in the TMS continued to receive 40 mg apremilast capsules BID for an additional 40 weeks during the active treatment phase. Participants who completed 52 weeks of treatment and had a Mayo endoscopy score ≤ 1 at week 52 were eligible to participate in the 52-week extension phase and receive 30 mg apremilast BID for an additional 52 weeks. This includes participants assigned to 30 mg apremilast BID at week 12, and participants who entered the extension phase after implementation of Protocol Amendment 4. Participants who completed 52 weeks of treatment and had a Mayo endoscopy score ≤ 1 at week 52 were eligible to participate in the 52-week extension phase and receive 40 mg apremilast BID for an additional 52 weeks. After implementation of Protocol Amendment 4 participants were switched to 30 mg apremilast BID for the remainder of the extension phase.
    Period Title: Placebo-Controlled Phase Weeks 0-12
    STARTED 58 57 55 0 0 0 0 0 0
    COMPLETED 51 53 52 0 0 0 0 0 0
    NOT COMPLETED 7 4 3 0 0 0 0 0 0
    Period Title: Placebo-Controlled Phase Weeks 0-12
    STARTED 0 41 42 26 25 12 7 0 0
    COMPLETED 0 39 32 17 20 7 5 0 0
    NOT COMPLETED 0 2 10 9 5 5 2 0 0
    Period Title: Placebo-Controlled Phase Weeks 0-12
    STARTED 0 0 0 0 0 0 0 45 54
    COMPLETED 0 0 0 0 0 0 0 38 48
    NOT COMPLETED 0 0 0 0 0 0 0 7 6

    Baseline Characteristics

    Arm/Group Title Placebo Apremilast 30 mg Apremilast 40 mg Total
    Arm/Group Description Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth PO BID for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. Total of all reporting groups
    Overall Participants 58 57 55 170
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    42.9
    (14.04)
    40.1
    (13.50)
    43.4
    (14.92)
    42.1
    (14.15)
    Sex: Female, Male (Count of Participants)
    Female
    25
    43.1%
    18
    31.6%
    21
    38.2%
    64
    37.6%
    Male
    33
    56.9%
    39
    68.4%
    34
    61.8%
    106
    62.4%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    2
    3.4%
    1
    1.8%
    5
    9.1%
    8
    4.7%
    Not Hispanic or Latino
    55
    94.8%
    54
    94.7%
    46
    83.6%
    155
    91.2%
    Unknown or Not Reported
    1
    1.7%
    2
    3.5%
    4
    7.3%
    7
    4.1%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    0
    0%
    0
    0%
    1
    1.8%
    1
    0.6%
    White
    54
    93.1%
    52
    91.2%
    45
    81.8%
    151
    88.8%
    Other
    1
    1.7%
    1
    1.8%
    1
    1.8%
    3
    1.8%
    Not Reported or Collected
    3
    5.2%
    4
    7%
    8
    14.5%
    15
    8.8%
    Duration of Ulcerative Colitis (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    6.85
    (7.043)
    6.15
    (5.432)
    8.63
    (10.278)
    7.19
    (7.832)
    Baseline Total Mayo Score (TMS) (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    8.2
    (1.68)
    8.5
    (1.62)
    8.1
    (1.67)
    8.3
    (1.65)
    Modified Mayo Score (MMS) (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    6.1
    (1.51)
    6.4
    (1.48)
    6.0
    (1.47)
    6.2
    (1.49)
    Partial Mayo Score (PMS) (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    5.6
    (1.46)
    5.8
    (1.44)
    5.5
    (1.57)
    5.6
    (1.49)
    Mayo Endoscopic Subscore (MES) (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    2.6
    (0.49)
    2.7
    (0.45)
    2.6
    (0.49)
    2.6
    (0.48)
    Baseline Use of Oral Corticosteroids (Number) [Number]
    Number [Participants]
    17
    29.3%
    14
    24.6%
    12
    21.8%
    43
    25.3%
    Previous Exposure to Use of Immunosuppressants (Number) [Number]
    Number [Participants]
    17
    29.3%
    18
    31.6%
    16
    29.1%
    51
    30%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants Who Achieved a Clinical Remission by Total Mayo Score (TMS) at Week 12
    Description Clinical remission was defined as a total Mayo score ≤ 2 points, with no individual subscore exceeding 1 point. The TMS is an instrument designed to measure disease activity of UC. The Mayo score ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease. Stool Frequency Subscore (SFS) Rectal Bleeding Subscore (RBS) Endoscopy Subscore Physician's Global Assessment (PGA). Two-sided 95% confidence intervals (CI) for the within-group percentages are based on the Wilson score method.
    Time Frame Week 12

    Outcome Measure Data

    Analysis Population Description
    The intent to treat (ITT) population included all participants who received at least one dose of IP. Participants with insufficient data for response determination were considered non-responders.
    Arm/Group Title Placebo Apremilast 30 mg Apremilast 40 mg
    Arm/Group Description Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
    Measure Participants 58 57 55
    Number (95% Confidence Interval) [Percentage of Participants]
    12.1
    20.9%
    31.6
    55.4%
    21.8
    39.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0142
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Stratification was based on baseline use of oral (PO) corticosteroids and previously used immunosuppressants (yes/no).
    Method of Estimation Estimation Parameter Stratified Difference
    Estimated Value 19.2
    Confidence Interval (2-Sided) 95%
    3.4 to 33.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 40 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2689
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
    Method of Estimation Estimation Parameter Stratified Difference
    Estimated Value 7.7
    Confidence Interval (2-Sided) 95%
    -6.9 to 22.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method
    2. Secondary Outcome
    Title Percentage of Participants Who Achieved a Clinical Response by Total Mayo Score and the Reduction in the Rectal Bleeding Subscore at Week 12
    Description Clinical response was defined as a decrease from baseline in the TMS of at least 3 points and at least 30%, along with a reduction in the rectal bleeding subscore (RBS) of at least 1 point or an absolute RBS of ≤ 1. The TMS is an instrument designed to measure disease activity of UC. The Mayo score ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease. Stool Frequency Subscore (SFS) Rectal Bleeding Subscore Endoscopy Subscore Physician's Global Assessment (PGA) Rectal bleeding (subscore 0-3) was defined as: 0 = No blood seen = Streaks of blood with stool less than half the time = Obvious blood with stool = Blood alone passes Two-sided 95% CI for the within-group percentages are based on the Wilson score method.
    Time Frame Week 12

    Outcome Measure Data

    Analysis Population Description
    The intent to treat (ITT) population included all participants who received at least one dose of IP. Participants with insufficient data for response determination were considered non-responders.
    Arm/Group Title Placebo Apremilast 30 mg Apremilast 40 mg
    Arm/Group Description Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
    Measure Participants 58 57 55
    Number (95% Confidence Interval) [Percentage of Participants]
    46.6
    80.3%
    61.4
    107.7%
    67.3
    122.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1224
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
    Method of Estimation Estimation Parameter Stratified Difference
    Estimated Value 14.6
    Confidence Interval (2-Sided) 95%
    -3.6 to 31.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 40 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0401
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
    Method of Estimation Estimation Parameter Stratified Difference
    Estimated Value 19.4
    Confidence Interval (2-Sided) 95%
    1.1 to 36.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
    3. Secondary Outcome
    Title Percentage of Participants Who Achieved an Endoscopic Remission at Week 12
    Description An endoscopic remission was defined as a Mayo endoscopic subscore (MES) of 0 at Week 12. The MES subscore findings were defined as: 0 = Normal or inactive disease = Mild Disease (erythema, decreased vascular pattern, mild friability) = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions) = Severe Disease (spontaneous bleeding, ulceration) The endoscopy subscores consisted of findings that were centrally read through proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method.
    Time Frame Week 12

    Outcome Measure Data

    Analysis Population Description
    The intent to treat population included all participants who received at least one dose of IP. Participants with insufficient data for response determination were considered non-responders.
    Arm/Group Title Placebo Apremilast 30 mg Apremilast 40 mg
    Arm/Group Description Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
    Measure Participants 58 57 55
    Number (95% Confidence Interval) [Percentage of Participants]
    3.4
    5.9%
    8.8
    15.4%
    7.3
    13.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2472
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
    Method of Estimation Estimation Parameter Stratified Difference
    Estimated Value 5.2
    Confidence Interval (2-Sided) 95%
    -5.7 to 16.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 40 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4628
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
    Method of Estimation Estimation Parameter Stratified Difference
    Estimated Value 3.1
    Confidence Interval (2-Sided) 95%
    -7.5 to 14.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
    4. Secondary Outcome
    Title Percentage of Participants Who Achieved an Endoscopic Response at Week 12
    Description An endoscopic response is defined as a decrease from baseline of at least 1 point in the MES at Week 12. The Mayo endoscopy subscore findings were defined as: 0 = Normal or inactive disease = Mild Disease (erythema, decreased vascular pattern, mild friability) = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions) 3 = Severe Disease (spontaneous bleeding, ulceration). The endoscopy subscores consisted of findings that were centrally read through proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method.
    Time Frame Week 12

    Outcome Measure Data

    Analysis Population Description
    The intent to treat population included all participants who received at least one dose of IP. Participants with insufficient data for response determination were considered non-responders.
    Arm/Group Title Placebo Apremilast 30 mg Apremilast 40 mg
    Arm/Group Description Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
    Measure Participants 58 57 55
    Number (95% Confidence Interval) [Percentage of Participants]
    41.4
    71.4%
    73.7
    129.3%
    47.3
    86%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0005
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
    Method of Estimation Estimation Parameter Stratified Difference
    Estimated Value 32.0
    Confidence Interval (2-Sided) 95%
    13.8 to 47.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 40 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6878
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
    Method of Estimation Estimation Parameter Stratified Difference
    Estimated Value 3.7
    Confidence Interval (2-Sided) 95%
    -14.4 to 21.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
    5. Secondary Outcome
    Title Percentage of Participants Who Achieved a Rectal Bleeding Subscore (RBS) of ≤ 1 at Week 12
    Description The RBS was measured as: 0 = No blood seen = Streaks of blood with stool less than half the time = Obvious blood with stool most of the time = Blood alone passes The daily bleeding score represents the most severe bleeding of the day. Two-sided 95% CI for the within-group proportions are based on the Wilson score method.
    Time Frame Week 12

    Outcome Measure Data

    Analysis Population Description
    The intent to treat population included all participants who received at least one dose of IP. Participants with insufficient data for response determination were considered non-responders.
    Arm/Group Title Placebo Apremilast 30 mg Apremilast 40 mg
    Arm/Group Description Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
    Measure Participants 58 57 55
    Number (95% Confidence Interval) [Percentage of Participants]
    72.4
    124.8%
    84.2
    147.7%
    87.3
    158.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1388
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
    Method of Estimation Estimation Parameter Stratified Difference
    Estimated Value 11.5
    Confidence Interval (2-Sided) 95%
    -4.1 to 26.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 40 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0788
    Comments Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Stratified Difference
    Estimated Value 13.5
    Confidence Interval (2-Sided) 95%
    -1.6 to 27.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
    6. Secondary Outcome
    Title Percentage of Participants Who Achieved Clinical Remission in the Modified Mayo Subscore (MMS) at Week 12
    Description Clinical remission was defined as a modified Mayo score of ≤ 2, with no individual subscore > 1, at Week 12. The MMS was based on a modification of the total Mayo score (TMS) which included the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the Physician's Global Assessment (PGA) subscore, since this was a global measure that is subjective in nature. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity. The endoscopy subscores was centrally reviewed. Two-sided confidence intervals for the within-group percentage were based on the Wilson score method.
    Time Frame Week 12

    Outcome Measure Data

    Analysis Population Description
    The intent to treat population included all participants who received at least one dose of IP. Participants with insufficient data for response determination were considered non-responders.
    Arm/Group Title Placebo Apremilast 30 mg Apremilast 40 mg
    Arm/Group Description Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
    Measure Participants 58 57 55
    Number (95% Confidence Interval) [Percentage of Participants]
    19.0
    32.8%
    43.9
    77%
    27.3
    49.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0046
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
    Method of Estimation Estimation Parameter Stratified Difference
    Estimated Value 24.8
    Confidence Interval (2-Sided) 95%
    7.5 to 40.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 40 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4476
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
    Method of Estimation Estimation Parameter Stratified Difference
    Estimated Value 6.0
    Confidence Interval () 95%
    -9.8 to 21.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
    7. Secondary Outcome
    Title Percentage of Participants Who Achieved Clinical Response in the Modified Mayo Subscore (MMS) at Week 12
    Description Clinical response in the MMS was defined as a decrease from baseline in the MMS of at least 2 points and at least 25%, along with a reduction in the RBS of at least 1 point or an absolute RBS ≤ 1. The MMS was based on the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the PGA subscore. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity. The RBS was measured as: 0 = No blood seen = Streaks of blood with stool less than half the time = Obvious blood with stool most of the time = Blood alone passes The daily bleeding score represents the most severe bleeding of the day. The endoscopy subscores was centrally reviewed. Two-sided confidence intervals for the within-group percentage were based on the Wilson score method.
    Time Frame Week 12

    Outcome Measure Data

    Analysis Population Description
    The intent to treat population included all participants who received at least one dose of IP. Participants with insufficient data for response determination were considered non-responders.
    Arm/Group Title Placebo Apremilast 30 mg Apremilast 40 mg
    Arm/Group Description Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
    Measure Participants 58 57 55
    Number (95% Confidence Interval) [Percentage of Participants]
    46.6
    80.3%
    63.2
    110.9%
    67.3
    122.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0755
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
    Method of Estimation Estimation Parameter Stratified Difference
    Estimated Value 16.7
    Confidence Interval (2-Sided) 95%
    -1.4 to 33.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 40 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0370
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
    Method of Estimation Estimation Parameter Stratified Difference
    Estimated Value 19.8
    Confidence Interval (2-Sided) 95%
    1.5 to 36.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
    8. Secondary Outcome
    Title Percentage of Participants Who Achieved Clinical Remission in the Partial Mayo Subscore (PMS) With no Individual Subscore >1 at Week 8
    Description Clinical remission in the partial Mayo subscore was defined as a PMS of 2 points or lower, with no individual subscore >1. The PMS is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease). Two-sided 95% CI for the within-group proportions are based on the Wilson score method.
    Time Frame Week 8

    Outcome Measure Data

    Analysis Population Description
    The intent to treat population included all participants who received at least one dose of IP. Participants with insufficient data for response determination were considered non-responders.
    Arm/Group Title Placebo Apremilast 30 mg Apremilast 40 mg
    Arm/Group Description Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
    Measure Participants 58 57 55
    Number (95% Confidence Interval) [Percentage of Participants]
    32.8
    56.6%
    47.4
    83.2%
    52.7
    95.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1167
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
    Method of Estimation Estimation Parameter Stratified Difference
    Estimated Value 14.6
    Confidence Interval (2-Sided) 95%
    -3.3 to 31.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 40 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0534
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
    Method of Estimation Estimation Parameter Stratified Difference
    Estimated Value 18.1
    Confidence Interval (2-Sided) 95%
    -0.3 to 34.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
    9. Secondary Outcome
    Title Percentage of Participants Who Achieved Clinical Response in the Partial Mayo Subscore at Week 8
    Description Clinical response in the PMS was defined as a decrease from baseline in PMS of at least 2 points and at least 25%, with an accompanying decrease in the RBS of at least 1 point or an absolute RBS of 0 or 1. The PMS score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease). Two-sided 95% CI for the within-group proportions are based on the Wilson score method.
    Time Frame Week 8

    Outcome Measure Data

    Analysis Population Description
    The intent to treat population included all participants who received at least one dose of IP. Participants with insufficient data for response determination were considered non-responders.
    Arm/Group Title Placebo Apremilast 30 mg Apremilast 40 mg
    Arm/Group Description Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
    Measure Participants 58 57 55
    Number (95% Confidence Interval) [Percentage of Participants]
    48.3
    83.3%
    64.9
    113.9%
    81.8
    148.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 30 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0758
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
    Method of Estimation Estimation Parameter Stratified Difference
    Estimated Value 16.6
    Confidence Interval (2-Sided) 95%
    -1.5 to 33.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Apremilast 40 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0004
    Comments
    Method Cochran-Mantel-Haenszel
    Comments Stratification was based on baseline use of PO corticosteroids and previously used immunosuppressants (yes/no).
    Method of Estimation Estimation Parameter Stratified Difference
    Estimated Value 32.5
    Confidence Interval (2-Sided) 95%
    14.9 to 47.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Stratified difference in percentages is the weighted average of the treatment differences across the strata with the CMH weights, with 2-sided 95% CI based on the stratified Newcombe method.
    10. Secondary Outcome
    Title The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase
    Description A TEAE was defined as any adverse event (AE) occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain
    Time Frame From the first dose of investigational product (IP) and no later than 28 days after the last dose of IP for those who had completed the study or discontinued (D/C) early; maximum duration of exposure to treatment was 12.00 weeks

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who were enrolled and received at least 1 dose of investigational product.
    Arm/Group Title Placebo Apremilast 30 mg Apremilast 40 mg
    Arm/Group Description Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
    Measure Participants 58 57 55
    Any TEAE
    31
    53.4%
    28
    49.1%
    36
    65.5%
    Any IP-related TEAE
    12
    20.7%
    13
    22.8%
    20
    36.4%
    Any Severe TEAE
    4
    6.9%
    0
    0%
    1
    1.8%
    Any Serious TEAE
    2
    3.4%
    0
    0%
    1
    1.8%
    Any Serious IP-related TEAE
    0
    0%
    0
    0%
    0
    0%
    Any TEAE Leading to IP Withdrawal
    5
    8.6%
    0
    0%
    1
    1.8%
    Any TEAE Leading to IP Interruption
    1
    1.7%
    0
    0%
    0
    0%
    Any TEAE Leading to Death
    0
    0%
    0
    0%
    0
    0%
    11. Secondary Outcome
    Title The Number of Participants Who Discontinued Apremilast Due to Treatment Emergent Adverse Events During the Placebo-Controlled Period
    Description A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain.
    Time Frame From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early; median duration of exposure to treatment was 12.00 weeks

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who were enrolled and received at least 1 dose of investigational product.
    Arm/Group Title Placebo Apremilast 30 mg Apremilast 40 mg
    Arm/Group Description Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
    Measure Participants 58 57 55
    Count of Participants [Participants]
    5
    8.6%
    0
    0%
    1
    1.8%
    12. Secondary Outcome
    Title The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52
    Description A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain
    Time Frame From first dose of IP and no later than 28 days after last dose of IP for those who completed the active treatment phase or D/C early; median duration of exposure = 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms

    Outcome Measure Data

    Analysis Population Description
    Apremilast exposure population included all participants who were randomized at Week 0 or assigned at Week 12 to an apremilast group and received at least 1 dose of apremilast.
    Arm/Group Title Apremilast 30 mg Apremilast 40 mg Apremilast 30 mg/Apremilast 40 mg
    Arm/Group Description TEAEs during the apremilast 30 mg BID treatment for participants who received 30 mg apremilast capsules BID only and participants who initially received 30 mg apremilast capsules BID and switched to 40 mg apremilast capsules BID at Week 12, and participants who initially received placebo capsules BID and switched to 30 mg apremilast capsules BID at Week 12. TEAEs during the apremilast 40 mg BID treatment for participants who received 40 mg apremilast capsules BID only, and participants who initially received placebo BID and switched to 40 mg apremilast capsules BID at Week 12. TEAEs during the apremilast 40 mg BID treatment for participants who initially received 30 mg apremilast BID and switched to apremilast 40 mg BID at Week 12.
    Measure Participants 83 80 11
    Any TEAE
    60
    103.4%
    67
    117.5%
    8
    14.5%
    Any Severe TEAE
    5
    8.6%
    6
    10.5%
    0
    0%
    Any Serious TEAE
    6
    10.3%
    8
    14%
    1
    1.8%
    Any TEAE Leading to Drug Withdrawal
    3
    5.2%
    9
    15.8%
    1
    1.8%
    Any TEAE Leading to Drug Interruption
    1
    1.7%
    4
    7%
    0
    0%
    Any TEAE Leading to Death
    0
    0%
    0
    0%
    0
    0%
    13. Secondary Outcome
    Title The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase)
    Description A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain
    Time Frame From the first dose of IP at Week 52 and no later than 28 days after the last dose of IP for those who completed the study or had discontinued early; median exposure of apremilast for the total apremilast group was 52 weeks.

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least 1 dose of apremilast after week 52.
    Arm/Group Title Extension Phase: Apremilast 30 mg Extension Phase: Apremilast 40 mg
    Arm/Group Description Participants who completed 52 weeks of treatment and had a Mayo endoscopy score ≤ 1 at week 52 were eligible to participate in the 52-week extension phase and received 30 mg apremilast BID for an additional 52 weeks. Includes participants assigned to 30 mg apremilast BID at week 12, and participants who entered the extension phase after implementation of Protocol Amendment 4. Participants who completed 52 weeks of treatment and had a Mayo endoscopy score ≤ 1 at week 52 were eligible to participate in the 52-week extension phase and received 40 mg apremilast BID for an additional 52 weeks. After implementation of Protocol Amendment 4, participants were switched to 30 mg apremilast BID for the remainder of the extension phase.
    Measure Participants 45 54
    Any TEAE
    16
    27.6%
    27
    47.4%
    Any Severe TEAE
    1
    1.7%
    0
    0%
    Any Serious TEAE
    4
    6.9%
    3
    5.3%
    Any Serious IP-related TEAE
    0
    0%
    1
    1.8%
    Any TEAE Leading to IP Withdrawal
    2
    3.4%
    1
    1.8%
    Any TEAE Leading to IP Interruption
    1
    1.7%
    0
    0%
    Any TEAE Leading to Death
    0
    0%
    0
    0%

    Adverse Events

    Time Frame From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104.
    Adverse Event Reporting Description Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
    Arm/Group Title Placebo (Placebo Controlled Period) Apremilast 30 mg (Placebo Controlled Period) Apremilast 40 mg BID (Placebo Controlled Period) Apremilast 30 mg (Apremilast Exposure Period) Apremilast 40 mg (Apremilast Exposure Period) Apremilast 30/40 mg (Apremilast Exposure Period)
    Arm/Group Description TEAEs for participants who were randomized to identically matching placebo capsules twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase. TEAEs for participants who were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. TEAEs for participants who were randomized to apremilast 40 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. TEAEs during the apremilast 30 mg BID treatment for participants who received 30 mg apremilast capsules BID only and participants who initially received 30 mg apremilast capsules BID and switched to 40 mg apremilast capsules BID at Week 12, and participants who initially received placebo capsules BID and switched to 30 mg apremilast capsules BID at Week 12. TEAEs during the apremilast 40 mg BID treatment for participants who received 40 mg apremilast capsules BID only, and participants who initially received placebo BID and switched to 40 mg apremilast capsules BID at Week 12. TEAEs during the apremilast 40 mg BID treatment for participants who initially received 30 mg apremilast BID and switched to apremilast 40 mg BID at Week 12. for participants who initially received 30 mg apremilast dosage and switched to 40 mg apremilast capsules BID at Week 12.
    All Cause Mortality
    Placebo (Placebo Controlled Period) Apremilast 30 mg (Placebo Controlled Period) Apremilast 40 mg BID (Placebo Controlled Period) Apremilast 30 mg (Apremilast Exposure Period) Apremilast 40 mg (Apremilast Exposure Period) Apremilast 30/40 mg (Apremilast Exposure Period)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/58 (0%) 0/57 (0%) 0/55 (0%) 0/83 (0%) 0/80 (0%) 0/11 (0%)
    Serious Adverse Events
    Placebo (Placebo Controlled Period) Apremilast 30 mg (Placebo Controlled Period) Apremilast 40 mg BID (Placebo Controlled Period) Apremilast 30 mg (Apremilast Exposure Period) Apremilast 40 mg (Apremilast Exposure Period) Apremilast 30/40 mg (Apremilast Exposure Period)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/58 (3.4%) 0/57 (0%) 1/55 (1.8%) 9/83 (10.8%) 11/80 (13.8%) 1/11 (9.1%)
    Cardiac disorders
    Acute myocardial infarction 0/58 (0%) 0/57 (0%) 0/55 (0%) 1/83 (1.2%) 0/80 (0%) 0/11 (0%)
    Congestive cardiomyopathy 0/58 (0%) 0/57 (0%) 0/55 (0%) 1/83 (1.2%) 0/80 (0%) 0/11 (0%)
    Gastrointestinal disorders
    Abdominal hernia 0/58 (0%) 0/57 (0%) 0/55 (0%) 0/83 (0%) 1/80 (1.3%) 0/11 (0%)
    Colitis ulcerative 2/58 (3.4%) 0/57 (0%) 0/55 (0%) 1/83 (1.2%) 3/80 (3.8%) 0/11 (0%)
    Crohn's disease 0/58 (0%) 0/57 (0%) 0/55 (0%) 0/83 (0%) 1/80 (1.3%) 0/11 (0%)
    Diarrhoea 0/58 (0%) 0/57 (0%) 0/55 (0%) 0/83 (0%) 1/80 (1.3%) 0/11 (0%)
    Inguinal hernia 0/58 (0%) 0/57 (0%) 0/55 (0%) 0/83 (0%) 0/80 (0%) 1/11 (9.1%)
    Pancreatitis 0/58 (0%) 0/57 (0%) 1/55 (1.8%) 0/83 (0%) 1/80 (1.3%) 0/11 (0%)
    Hepatobiliary disorders
    Cholecystitis 0/58 (0%) 0/57 (0%) 0/55 (0%) 1/83 (1.2%) 0/80 (0%) 0/11 (0%)
    Infections and infestations
    Clostridium difficile infection 0/58 (0%) 0/57 (0%) 0/55 (0%) 1/83 (1.2%) 0/80 (0%) 0/11 (0%)
    Epididymitis tuberculous 0/58 (0%) 0/57 (0%) 0/55 (0%) 0/83 (0%) 1/80 (1.3%) 0/11 (0%)
    Pilonidal cyst 0/58 (0%) 0/57 (0%) 0/55 (0%) 1/83 (1.2%) 0/80 (0%) 0/11 (0%)
    Rectal abscess 0/58 (0%) 0/57 (0%) 0/55 (0%) 0/83 (0%) 1/80 (1.3%) 0/11 (0%)
    Urinary tract infection 0/58 (0%) 0/57 (0%) 0/55 (0%) 1/83 (1.2%) 0/80 (0%) 0/11 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/58 (0%) 0/57 (0%) 0/55 (0%) 1/83 (1.2%) 0/80 (0%) 0/11 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Epididymal neoplasm 0/58 (0%) 0/57 (0%) 0/55 (0%) 0/83 (0%) 1/80 (1.3%) 0/11 (0%)
    Renal and urinary disorders
    Nephrolithiasis 0/58 (0%) 0/57 (0%) 0/55 (0%) 1/83 (1.2%) 0/80 (0%) 0/11 (0%)
    Renal colic 0/58 (0%) 0/57 (0%) 0/55 (0%) 1/83 (1.2%) 2/80 (2.5%) 0/11 (0%)
    Reproductive system and breast disorders
    Menorrhagia 0/58 (0%) 0/57 (0%) 0/55 (0%) 0/83 (0%) 1/80 (1.3%) 0/11 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo (Placebo Controlled Period) Apremilast 30 mg (Placebo Controlled Period) Apremilast 40 mg BID (Placebo Controlled Period) Apremilast 30 mg (Apremilast Exposure Period) Apremilast 40 mg (Apremilast Exposure Period) Apremilast 30/40 mg (Apremilast Exposure Period)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 20/58 (34.5%) 26/57 (45.6%) 25/55 (45.5%) 49/83 (59%) 53/80 (66.3%) 11/11 (100%)
    Blood and lymphatic system disorders
    Anaemia 1/58 (1.7%) 1/57 (1.8%) 0/55 (0%) 4/83 (4.8%) 4/80 (5%) 0/11 (0%)
    Gastrointestinal disorders
    Dyspepsia 1/58 (1.7%) 1/57 (1.8%) 0/55 (0%) 2/83 (2.4%) 0/80 (0%) 1/11 (9.1%)
    Nausea 5/58 (8.6%) 3/57 (5.3%) 6/55 (10.9%) 8/83 (9.6%) 9/80 (11.3%) 3/11 (27.3%)
    Abdominal pain 1/58 (1.7%) 3/57 (5.3%) 0/55 (0%) 4/83 (4.8%) 3/80 (3.8%) 1/11 (9.1%)
    Anorectal discomfort 0/58 (0%) 0/57 (0%) 0/55 (0%) 0/83 (0%) 0/80 (0%) 1/11 (9.1%)
    Colitis ulcerative 1/58 (1.7%) 0/57 (0%) 0/55 (0%) 2/83 (2.4%) 6/80 (7.5%) 0/11 (0%)
    Diarrhoea 2/58 (3.4%) 1/57 (1.8%) 0/55 (0%) 5/83 (6%) 6/80 (7.5%) 2/11 (18.2%)
    Gastritis 0/58 (0%) 0/57 (0%) 0/55 (0%) 1/83 (1.2%) 4/80 (5%) 0/11 (0%)
    Inguinal hernia 0/58 (0%) 0/57 (0%) 0/55 (0%) 0/83 (0%) 0/80 (0%) 1/11 (9.1%)
    Swollen tongue 0/58 (0%) 0/57 (0%) 0/55 (0%) 0/83 (0%) 0/80 (0%) 1/11 (9.1%)
    Vomiting 1/58 (1.7%) 2/57 (3.5%) 2/55 (3.6%) 3/83 (3.6%) 3/80 (3.8%) 3/11 (27.3%)
    General disorders
    Asthenia 2/58 (3.4%) 3/57 (5.3%) 1/55 (1.8%) 5/83 (6%) 3/80 (3.8%) 2/11 (18.2%)
    Influenza like illness 0/58 (0%) 1/57 (1.8%) 1/55 (1.8%) 2/83 (2.4%) 2/80 (2.5%) 1/11 (9.1%)
    Pyrexia 2/58 (3.4%) 1/57 (1.8%) 1/55 (1.8%) 1/83 (1.2%) 2/80 (2.5%) 2/11 (18.2%)
    Infections and infestations
    Upper respiratory tract infection 2/58 (3.4%) 1/57 (1.8%) 0/55 (0%) 4/83 (4.8%) 4/80 (5%) 0/11 (0%)
    Gastroenteritis 1/58 (1.7%) 0/57 (0%) 0/55 (0%) 3/83 (3.6%) 3/80 (3.8%) 1/11 (9.1%)
    Influenza 1/58 (1.7%) 0/57 (0%) 1/55 (1.8%) 2/83 (2.4%) 3/80 (3.8%) 1/11 (9.1%)
    Nasopharyngitis 1/58 (1.7%) 4/57 (7%) 2/55 (3.6%) 7/83 (8.4%) 8/80 (10%) 2/11 (18.2%)
    Periodontitis 0/58 (0%) 1/57 (1.8%) 0/55 (0%) 1/83 (1.2%) 0/80 (0%) 1/11 (9.1%)
    Pneumonia 0/58 (0%) 0/57 (0%) 1/55 (1.8%) 1/83 (1.2%) 1/80 (1.3%) 1/11 (9.1%)
    Sinusitis 0/58 (0%) 1/57 (1.8%) 0/55 (0%) 4/83 (4.8%) 0/80 (0%) 1/11 (9.1%)
    Investigations
    Blood lactate dehydrogenase increased 0/58 (0%) 0/57 (0%) 0/55 (0%) 0/83 (0%) 0/80 (0%) 1/11 (9.1%)
    Faecal calprotectin increased 0/58 (0%) 1/57 (1.8%) 1/55 (1.8%) 1/83 (1.2%) 1/80 (1.3%) 1/11 (9.1%)
    Metabolism and nutrition disorders
    Decreased appetite 1/58 (1.7%) 2/57 (3.5%) 1/55 (1.8%) 2/83 (2.4%) 3/80 (3.8%) 1/11 (9.1%)
    Iron deficiency 0/58 (0%) 0/57 (0%) 0/55 (0%) 0/83 (0%) 2/80 (2.5%) 1/11 (9.1%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/58 (3.4%) 0/57 (0%) 1/55 (1.8%) 5/83 (6%) 6/80 (7.5%) 1/11 (9.1%)
    Back pain 1/58 (1.7%) 0/57 (0%) 3/55 (5.5%) 0/83 (0%) 3/80 (3.8%) 0/11 (0%)
    Osteochondrosis 0/58 (0%) 1/57 (1.8%) 0/55 (0%) 1/83 (1.2%) 0/80 (0%) 1/11 (9.1%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Angiomyolipoma 0/58 (0%) 1/57 (1.8%) 0/55 (0%) 1/83 (1.2%) 0/80 (0%) 1/11 (9.1%)
    Nervous system disorders
    Headache 4/58 (6.9%) 12/57 (21.1%) 14/55 (25.5%) 17/83 (20.5%) 25/80 (31.3%) 2/11 (18.2%)
    Migraine 0/58 (0%) 1/57 (1.8%) 1/55 (1.8%) 2/83 (2.4%) 3/80 (3.8%) 1/11 (9.1%)
    Sciatica 0/58 (0%) 1/57 (1.8%) 0/55 (0%) 1/83 (1.2%) 1/80 (1.3%) 1/11 (9.1%)
    Sinus headache 0/58 (0%) 1/57 (1.8%) 0/55 (0%) 1/83 (1.2%) 0/80 (0%) 1/11 (9.1%)
    Psychiatric disorders
    Depressed mood 0/58 (0%) 0/57 (0%) 1/55 (1.8%) 2/83 (2.4%) 4/80 (5%) 0/11 (0%)
    Depression 1/58 (1.7%) 0/57 (0%) 1/55 (1.8%) 0/83 (0%) 1/80 (1.3%) 1/11 (9.1%)
    Insomnia 0/58 (0%) 2/57 (3.5%) 1/55 (1.8%) 3/83 (3.6%) 2/80 (2.5%) 1/11 (9.1%)
    Renal and urinary disorders
    Haematuria 0/58 (0%) 0/57 (0%) 0/55 (0%) 0/83 (0%) 0/80 (0%) 1/11 (9.1%)
    Respiratory, thoracic and mediastinal disorders
    Cough 1/58 (1.7%) 0/57 (0%) 1/55 (1.8%) 0/83 (0%) 5/80 (6.3%) 0/11 (0%)
    Dysphonia 0/58 (0%) 0/57 (0%) 0/55 (0%) 0/83 (0%) 0/80 (0%) 1/11 (9.1%)
    Nasal congestion 0/58 (0%) 1/57 (1.8%) 0/55 (0%) 1/83 (1.2%) 0/80 (0%) 1/11 (9.1%)
    Respiratory tract congestion 0/58 (0%) 1/57 (1.8%) 0/55 (0%) 1/83 (1.2%) 0/80 (0%) 1/11 (9.1%)
    Rhinitis allergic 0/58 (0%) 0/57 (0%) 0/55 (0%) 0/83 (0%) 0/80 (0%) 1/11 (9.1%)
    Rhinorrhoea 0/58 (0%) 1/57 (1.8%) 0/55 (0%) 1/83 (1.2%) 0/80 (0%) 1/11 (9.1%)
    Skin and subcutaneous tissue disorders
    Eczema 0/58 (0%) 0/57 (0%) 1/55 (1.8%) 1/83 (1.2%) 2/80 (2.5%) 1/11 (9.1%)
    Pruritus 0/58 (0%) 0/57 (0%) 0/55 (0%) 0/83 (0%) 2/80 (2.5%) 1/11 (9.1%)
    Rash 0/58 (0%) 1/57 (1.8%) 0/55 (0%) 1/83 (1.2%) 1/80 (1.3%) 1/11 (9.1%)
    Vascular disorders
    Angiopathy 0/58 (0%) 1/57 (1.8%) 0/55 (0%) 1/83 (1.2%) 0/80 (0%) 1/11 (9.1%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Results from a center cannot be submitted for publication before results of multicenter study are published unless it is > 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 additional days. Investigator must delete confidential information before submission and defer publication to permit patent applications.

    Results Point of Contact

    Name/Title Anne McClain, Senior Manager, Clinical Trial Disclosure
    Organization Celgene Corporation
    Phone 888-260-1599
    Email ClinicalTrialDisclosure@Celgene.com
    Responsible Party:
    Amgen
    ClinicalTrials.gov Identifier:
    NCT02289417
    Other Study ID Numbers:
    • CC-10004-UC-001
    • 2014-002981-64
    First Posted:
    Nov 13, 2014
    Last Update Posted:
    May 7, 2020
    Last Verified:
    Apr 1, 2020